January 29, 2015
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Oseltamivir reduced influenza symptoms, complications in adults

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An independent research group found that oseltamivir shortened the duration of influenza symptoms by approximately 1 day and reduced the risk for influenza complications requiring antibiotics by 44%, including pneumonia.

“This is the first patient-level analysis of how well this drug works,” Arnold S. Monto, MD, the Thomas Francis Jr. Collegiate Professor of Public Health at the University of Michigan School of Health, said in a press release. “Previous research has questioned its success and use in light of the side effects of nausea and vomiting, but the other studies combined those infected with influenza and those without, which diluted the positive effect in treatment.”

Arnold S. Monto

The 2014-2015 influenza season has been particularly severe, with vaccine efficacy as low as 23%. In January, the CDC recommended the use of antiviral drugs for the treatment of influenza, regardless of a patient’s vaccination status or confirmatory test results.

“Since oseltamivir [Tamiflu, Genentech] works best when given early in the course of an illness, we agree with the CDC that it should be given on the presumption of a case being influenza when there are appropriate symptoms during the influenza season,” Monto told Infectious Disease News. “Waiting for an absolute diagnosis would be a mistake, given the relatively low frequency of side effects. This particularly applies to individuals with risk conditions who are most likely to develop complications.”

Oseltamivir clinical trial data

Monto and colleagues performed a meta-analysis of published and unpublished randomized clinical trials conducted from 1997 to 2001 — made available through Roche, the drug’s manufacturer — to determine the efficacy of oseltamivir. Results of the analysis were published in The Lancet.

The researchers evaluated nine clinical trials involving 4,328 patients, with more than half of those receiving oseltamivir. Most of the infected population had influenza A(H3N2) — this influenza season’s predominant strain.

They found that when prescribed at a dosage of 75 mg twice daily for adults, oseltamivir reduced the time to alleviation of all symptoms by 21% compared with placebo (P<.0001). The estimated median time to alleviation of all symptoms was 97.5 hours for oseltamivir and 122.7 hours for placebo.

In addition to reducing the risk for lower respiratory tract complications arising more than 48 hours after study entry (RR=0.56; 95% CI, 0.42-0.75), oseltamivir reduced hospitalizations for any cause by 63% (RR=0.37; 95% CI, 0.17-0.81).

There was no noticeable benefit of oseltamivir in symptomatic adults without influenza infection, demonstrating oseltamivir’s role as an antiviral agent. However, these adults were at the same risk for adverse events as patients with confirmed influenza infection.

Risks vs. benefits of oseltamivir

Consistent with previous research, Monto and colleagues noted “highly significant” increases in nausea (absolute increase, 3.7%) and vomiting (4.7%) associated with oseltamivir. However, they did not find any differences in the development of neurological or psychological disorders between patients taking oseltamivir and placebo, although these disorders have been linked to the antiviral in other studies.

“The safety and effectiveness of oseltamivir has been hotly debated, with some researchers claiming there is little evidence that oseltamivir works,” Monto said in the release. “Our meta-analysis provides compelling evidence that oseltamivir therapy reduces by 1 day the typical length of illness in adults infected with influenza and also prevents complications and reduces the number of people needing hospital treatment. Whether the magnitude of these benefits outweigh the harms of nausea and vomiting needs careful consideration.”

Another recent meta-analysis of the efficacy of oseltamivir, published in 2014 by the Cochrane group, showed only a modest benefit with oseltamivir for patients with influenza-like illness and confirmed influenza virus infection — raising the question of whether the drug’s adverse events outweigh its benefits. However, the Cochrane study did not include individual patient data like the present analysis.

In a related editorial, Heath Kelly, MPH, adjunct professor of infectious disease at the Australian National University in Canberra, and Benjamin J. Cowling, PhD, associate professor and head of the division of epidemiology and biostatistics at the University of Hong Kong, argued that rapid diagnostic testing should be used when available before administering oseltamivir to patients in routine clinical care, although they noted this would be impractical in certain situations.

“In a pandemic or severe epidemic, oseltamivir can be used presumptively when there is a high probability that influenza-like illness is caused by influenza virus infection and when the outcome of infection is likely to be severe, but a proven strategy for rapid distribution needs to accompany any plan that proposes widespread use of oseltamivir,” they wrote. — John Schoen

For more information:

Dobson J. Lancet. 2015;doi:10.1016/S0140-6736(14)62449-1.

Jefferson T. BMJ. 2014;348:g2545.

Kelly H. Lancet. 2015;doi:10.1016/S0140-6736(15)60074-5.

Disclosure: Monto reports receiving fees from Biocryst and Roche unrelated to the study. See the study for a full list of financial disclosures from the other researchers. Cowling received research funding from MedImmune and Sanofi Pasteur and consults for Crucell. Kelly reports no relevant financial disclosures.